Proline and its derivatives are useful for the catalytic activation of carbonyl compounds, via nucleophilic enamine catalysis. Several important carbon-carbon bond forming reactions including the Mannich and Michael reactions have been developed using this approach.
List et al showed the proline catalyzed Mannich reaction of acetaldehyde to yield β-aminoaldehydes in high ees, which are desirable products as drug intermediates and in the synthesis of other biologically active molecules.
Compounds with amine functionality at the C-1 position of an indane or tetraline framework have received considerable attention as potential medical agents because of their interesting pharmacological properties.
(+)-Sertraline and Tametraline are the class of 1-aminoaryltetralins most of which have anti depressant activity, especially (+)-sertraline is a potent competitive selective serotinin reuptake inhibitor, which has become a commonly prescribed pharmaceutical for the treatment of depression and other anxiety related disorders. In 2004, it was the ninth top selling drug worldwide, also has become a popular target for asymmetric synthesis due to its small but challenging structure.
Tametraline, a catecholamine reuptake inhibitor, is the parent of a series of chemical compounds investigated by Pfizer that eventually led to the development of sertraline.

Many reports are available for the synthesis of (+)-sertraline due to its high pharmaceutical importance as a drug.
In an article by Welch et al in J. Med. Chem. 1984, 27, 1508, is disclosed synthesis of racemic sertraline.
According to the procedure, α,β-unsaturated ester was prepared by base catalyzed Stobbe condensation of 3,4-dichlorobenzophenone with diethylsuccinate. Ester was then subjected to acid-catalyzed decarboxylation, followed by catalytic hydrogenation (5% Pd/C) to give the saturated acid. Acid underwent cyclization under Friedel-Crafts' condition (anhyd. AlCl3) to produce tetralone. Finally, reductive amination of tetralone with methylamine (MeNH2, TiCl4; NaBH4, MeOH) afforded (+)-sertraline 1.
Chandrashekar et al. in Tetrahedron, 2000, 56, 1111 have disclosed the synthesis of (+)-sertraline (1a) by employing chiral pool strategy. Thus, reduction of ester with LiAlH4 gave alcohol, which was oxidized to aldehyde under Swern's conditions. Aldehyde on subsequent treatment with Wittig reagent namely PPh3=CHCO2Et to afforded α,β-unsaturated ester in 72% yield. The complete reduction of α,β-unsaturated ester gave the saturated alcohol. Oxidation of alcohol with Corey's reagent (PCC) followed by its treatment with Grignard reagent, i.e 3,4-dichlorophenylmagnesium bromide, gave the secondary alcohol in 83% yield. Alcohol was cyclized intramolecularly with anhyd. AlCl3, which generated with a second chiral centre of separable diastereomers. The conversion of cis isomer to (+)-sertraline (1a) was achieved via a known series of reactions namely debenzylation, Boc-protection, N-methylation and Boc-deprotection. Zhao et. al in Tetrahedron: Asymmetry, 2006, 17, 2074 approach (2006) discloses synthesis of racemic sertraline comprising subjecting racemic (±)-tetralone to reduction using L-proline derived catalyst and Me2S.BH3 to give diasteromers which were readily separated. The oxidation of trans isomer with PCC gave the optically active (+)-tetralone, which was transformed to (+)-sertraline via reductive amination.
(MeNH2, TiCl4, Raney-Ni) Chen et al. on Org. Lett. 1999, 1, 293 have achieved the synthesis of (+)-sertraline by the addition of Grignard reagent onto α,β-unsaturated chiral carbamate to provide in 90% yield. Reductive removal of chiral auxiliary in using NaBH4 in THF-H2O gave alcohol. Alcohol was transformed to iodoaldehyde in 85% yield. Iodoaldehyde on treatment with methylamine gave the corresponding imine which was subjected to BuLi-mediated intramolecular ring closing so that a single diastereomer of (+)-sertraline (1a) was obtained Lautens et al. in J. Am. Chem. Soc. 2005, 127, 15028. have reported the synthesis of (+)-sertraline (1) by employing Diels-Alder reaction between benzenediazonium-2-carboxylate, a benzyne-equivalent and dienyl ester in 1,2-dichloroethane as solvent at 60° C., to give the cycloadduct in 78% yield. Cycloadduct was hydrogenated and the benzyl group deprotected in one-pot using 10% Pd/C and H2 (4 atm) to give acid. The acid was then subjected to Curtius rearrangement via the initial formation of acylazide (ClCO2Et, then NaN3) followed by the addition of allyl alcohol at 90° C., which afforded allyl carbamate. N-methylation and deprotection of allyl group in resulted in the formation of (+)-sertraline 1.
U.S. Pat. No. 6,593,496 relates to a process for preparing the (+) enantiomer of N-[4(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine by reacting the (+) enantiomer of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone with monomethylamine and titanium chloride or molecular sieves.
U.S. Pat. No. 4,536,518 disclose the synthesis of cis (1S,4S)-sertraline which includes condensation of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-napthalenone with monomethylamine catalysed by TiCl4.
US2007260090 relates to a process for highly stereoselective synthesis of sertraline and sertraline intermediate. The mixture of 4-(3,4-Dichlorophenyl)-3,4-dihydro-N-methyl-1(2H)-naphthalenimine, 5% Pd/CaCO3, water and methanol was taken in a hydrogenation flask and then subjected to hydrogenation under a hydrogen pressure of 0.5 Kg at 20-35 DEG C. for 3 hours 30 minutes. The catalyst was removed by filtration and the solvent evaporated to obtain cis-(+−)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-naphthalen amine. (trans-(+−): 0.2). It is further disclosed that resolution of the racemic mixture was carried using D(−)mandelic acid to obtain cis-isomer.
The processes described in the art are lengthy, employ large amount of chemicals, additional step of resolution and expensive transition catalysts, often resulting in poor product selectivities which make the processes industrially not feasible.
Hence, there remains a need in the art to develop a concise, cost effective route for synthesis of amino aryl tetralines viz. (+)-sertraline and tametraline with excellent enantioselectivity.